0000000000073742
AUTHOR
Celine Gonthier
Regulation of Farnesyl Diphosphate Synthase Gene Expression by Fatty Acids
Cholesterol biosynthesis depends on the activity of regulatory enzymes, including the peroxisomal Farnesyl Diphosphate Synthase (FPPS ). Cholesterol regulates its own synthesis rate. Hence, as a response to cholesterol depletion, a feed back mechanism is activated, whereby sterol regulatory binding proteins (SREBPla, 1c and 2 ) are subjected to sequential proteolytic activation, which permits their interaction with specific DNA response elements from responsive genes. In turn, the transcriptional activity of cholesterol biosynthesis genes is induced. Conversely, cholesterol accumulation decreases SREBP maturation and transcription of controlled genes. In addition, polyunsaturated fatty acid…
Hepatic farnesyl diphosphate synthase expression is suppressed by polyunsaturated fatty acids
Dietary vegetable oils and fish oils rich in PUFA (polyunsaturated fatty acids) exert hypocholesterolaemic and hypotriglyceridaemic effects in rodents. The plasma cholesterol-lowering properties of PUFA are due partly to a diminution of cholesterol synthesis and of the activity of the rate-limiting enzyme HMG-CoA reductase (3-hydroxy-3-methylglutaryl-CoA reductase). To better understand the mechanisms involved, we examined how tuna fish oil and individual n−3 and n−6 PUFA affect the expression of hepatic FPP synthase (farnesyl diphosphate synthase), a SREBP (sterol regulatory element-binding protein) target enzyme that is subject to negative-feedback regulation by sterols, in co-ordination …